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Functional decline among patients with mental illness is not unique to individuals with psychotic disorders. Despite this, research on early predictors of functional outcome mainly focused on individuals thought to have an ‘at risk mental state’ (ARMS) for psychosis. There is evidence suggesting that certain early vulnerability markers, such as neurological soft signs (NSS), may explain variability in functional outcomes independent of the level of psychosis risk and the traditional diagnostic classification.

Method

Structural equation modeling was applied to baseline data from a prospective longitudinal study of 138 young individuals in treatment with secondary services for non-psychotic disorders. We evaluated theoretically based models of pathways to functional outcome starting from NSS. The intervening variables were established according to previous evidence and drawn from two general categories: cognition (neuro- and social-) and negative symptoms (expressive and experiential).

Results

A final trimmed model was a single path running from NSS to neurocognition to experiential negative symptoms to outcome. It could not be improved by adding or dropping connections that would change the single path to multiple paths. The indirect effect from NSS to outcome was significant. The validity of the model was independent of the ARMS status and the psychiatric diagnosis.

Conclusions

Our results provide evidence for a single pathway model in which the starting and intervening variables represent modifiable trans-diagnostic therapeutic targets to improve functional trajectories in young individuals with a recent-onset psychiatric diagnosis and different levels of psychosis risk.

A series of research reports has indicated that the use of substances such as cannabis, alcohol and tobacco are higher in youth at clinical high risk (CHR) of developing psychosis than in controls. Little is known about the longitudinal trajectory of substance use, and findings on the relationship between substance use and later transition to psychosis in CHR individuals are mixed.

Method

At baseline and 6- and 12-month follow-ups, 735 CHR and 278 control participants completed the Alcohol and Drug Use Scale and a cannabis use questionnaire. The longitudinal trajectory of substance use was evaluated with linear mixed models.

Results

CHR participants endorsed significantly higher cannabis and tobacco use severity, and lower alcohol use severity, at baseline and over a 1-year period compared with controls. CHR youth had higher lifetime prevalence and frequency of cannabis, and were significantly younger upon first use, and were more likely to use alone and during the day. Baseline substance use did not differentiate participants who later transitioned to psychosis (n = 90) from those who did not transition (n = 272). Controls had lower tobacco use than CHR participants with a prodromal progression clinical outcome and lower cannabis use than those with a psychotic clinical outcome at the 2-year assessment.

Conclusions

In CHR individuals cannabis and tobacco use is higher than in controls and this pattern persists across 1 year. Evaluation of clinical outcome may provide additional information on the longitudinal impact of substance use that cannot be detected through evaluation of transition/non-transition to psychosis alone.

Patients with schizophrenia consistently demonstrate information processing abnormalities assessed with visual masking (VM) tasks, and these deficits have been linked to clinical and functional severity. It has been suggested that VM impairments may be a vulnerability marker in individuals at risk for developing psychosis.

Method

Forward and backward VM performance was assessed in 72 first-episode (FE) psychosis patients, 98 subjects at risk (AR) for psychosis and 98 healthy controls (HC) using two identification tasks (with either a high- or low-energy mask) and a location task. VM was examined for stability in a subgroup (FE, n=15; AR, n=35; HC, n=21) and assessed relative to clinical and functional measures.

Results

In the identification tasks, backward VM deficits were observed in both FE and AR relative to HC whereas forward VM deficits were only present in FE patients compared to HC. In the location task, AR subjects demonstrated superior performance in forward VM relative to HC. VM performance was stable over time, and VM deficits were associated with baseline functional measures and predicted future negative symptom severity in AR subjects.

Conclusions

Visual information processing deficits, as indexed by backward VM, are present before and after the onset of frank psychosis, and probably represent a stable vulnerability marker that is associated with negative symptoms and functional decline. Additionally, the paradoxically better performance of AR subjects in select forward tasks suggests that early compensatory changes may characterize an emerging psychotic state.

Deficits in automatic sensory discrimination, as indexed by a reduction in the mismatch negativity (MMN) and P3a event-related potential amplitudes, are well documented in chronic schizophrenia. However, MMN and P3a have not been sufficiently studied early in the course of psychotic illness. The present study aimed to investigate MMN, P3a and reorienting negativity (RON) across the course of schizophrenia.

Frontocentral deficits in MMN and P3a were present in all patient groups. The at-risk group's MMN and P3a amplitudes were intermediate to those of the control and recent-onset groups. The recent-onset and chronic patients, but not the at-risk subjects, showed significant RON amplitude reductions, relative to the control group. Associations between MMN, P3a, RON and psychosocial functioning were present in the chronic patients. In the at-risk subjects, P3a and RON deficits were significantly associated with higher levels of negative symptoms.

Conclusions

Abnormalities in the automatic processes of sensory discrimination, orienting and reorienting of attention are evident in the early phases of schizophrenia and raise the possibility of progressive worsening across stages of the illness. The finding that MMN and P3a, but not RON, were reduced before psychosis onset supports the continued examination of these components as potential early biomarkers of schizophrenia.

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